A micelle is a colloidal aggregate of amphipathic molecules containing both hydrophilic and hydrophobic moieties. In polar media, such as water, the hydrophobic part of the amphiphile forming the micelle tends to locate away from the polar portion, while the polar portion of the molecule also known as the head group tends to locate at the polar micelle water (solvent) interface. On the other hand, micelles may also be formed in non-polar media, such as non-polar organic solvents, e.g., hexane, whereby the amphiphilic cluster around the small water droplets is in the center of the system. In non-polar media, the hydrophobic moieties are exposed to the non-polar media, while the hydrophilic portion tends to locate away from the solvent and towards the water droplets. Such an assembly is sometimes referred to as a reversed micelle. These two aforementioned systems represent water-in-oil and oil-in-water, respectively, types of systems.
A micelle may take several forms, depending on the conditions and the composition of the system. For example, small micelles in dilute solution at approximately the critical micelle concentration (CMC) are generally believed to be spherical. However, under other conditions, they may be in the shape of distorted spheres, disks, rods, lamellae, and the like.
Micelles are formed at a critical micelle concentration (CMC) which is dependent upon several factors, including the type of amphipathic molecule, the solvent system, solute and the like. The critical micelle concentration denotes the concentration at which micelles start to form in a system containing solvent, amphiphatic molecule, and solute and the like. The CMC can be determined experimentally using standard techniques in the art. For example, the CMC of a surfactant can be determined by plotting a property as a function of the concentration of the surfactant; it is noted that the property usually varies linearly with increasing concentration up to the CMC, at which point the curve becomes non-linear. Properties which have been used for the determination of the CMC include such properties as refractive index, light scattering, dialysis, surface tension and dye solution.
Micellar properties are affected by the environment and more specifically changes in the environment, e.g., temperature, solvents, solubilized components, electrolytes in the system and the like. The prior art has described micelles whose properties have been exploited.
For example, U.S. Pat. No. 5,929,177 to Kataoka, et al. describes a polymeric molecule which is usable as, inter alia, a drug delivery carrier. The micelle is formed from a block copolymer having functional groups on both of its ends and which comprises hydrophilic/hydrophobic segments. The polymer functional groups on the ends of the block copolymer include amino, carboxyl and mercapto groups on the α-terminal and hydroxyl, carboxyl group, aldehyde group and vinyl group on the ω-terminal. The hydrophilic segment comprises polyethylene oxide, while the hydrophobic segment is derived from lactide, lactone or (meth)acrylic acid ester.
U.S. Pat. No. 5,925,720 to Kataoka, et al. provides a heterotelechelic oligomer or polymer of the formula:
wherein                R1 and R2 combined with each other denoted C1-10 alkoxy, aryloxy or aryl C1-3 alkoxy or oxy (═O), or R1 and R2 independently denote ethylenedioxy, O—CH(R1)—CH2—O—;        R1 denotes hydrogen or C1-6 alkyl;        L is        
                R3 and R4 independently denote hydrogen, alkyl, aryl or arylalkyl;        r is 2-5;        m is 2-10,000;        n is 2-10,000;        p is 1-5;        q is 0-20;        when q is 0, Z denotes H, alkali metal, acetyl, acryloxyl, methacryloyl, cinnamoyl, p-toluenesulfonyl, 2-mercaptopropionyl or 2-aminopropionyl or allyl or vinylbenzyl,        when q is 1-20, Z is C1-6 alkoxycarbonyl, carboxyl, mercapto or amino.        
This oligomer or polymer forms a high-molecular micelle which is stable in aqueous solvent and is useful as a carrier for drug delivery.
In neither of these references was the micelle used as a coating.
However, other types of non-micellar polymers have been used to coat surfaces. For example, U.S. Pat. No. 5,275,838 to Merrill discloses a method for immobilizing polyethylene oxide (PEO) stat molecules in the form of hydrogel layers and the product thereof which can be used to coat surfaces. It describes a method for immobilizing polyethylene oxide star molecules to a support surface to form a layer thereon, comprising the steps of:
(a) exposing an organic solution comprising polyethylene oxide star molecules, each of which consists essentially of a plurality of hydroxy terminated polyethylene oxide chains to a divinyl benzene core, to a reagent to affix reagent groups to the hydroxy termini, said reagent groups permitting subsequent attachment of amino or thiol groups to the PEO chain ends by displacement, thereby forming activated polyethylene oxide star molecules with active reagent end groups;
(b) separating the activated polyethylene oxide star molecules with active reagent end groups from the organic solvent;
(c) dissolving the activated polyethylene oxide star molecules in an aqueous solution; and
(d) contacting the solution of step (c) with a support surface containing amino and/or thiol groups to covalently bond the reagent terminated star molecules, thereby immobilizing the reagent terminated star molecules in a dense layer to the support surface.
The star molecules have a polymeric core, such as divinyl benzene, from which a number of polyethylene oxide chains or arms are grown. These star molecules are not micelles. They are not comprised of block copolymers having HLB (hydrophilic-lipophilic balance) of 1-40. As described therein, the star molecules are synthesized by anionic polymerization from divinyl benzene, ethylene oxide and optionally styrene.
The present invention utilizes different types of compounds and coating technology than those described in Merrill. Unlike Merrill, the coating composition of the present invention are comprised of micelles. As explained hereinbelow, the micelles utilized in the present invention are comprised of block copolymers having an HLB value ranging from 1-40. The present inventors have found coating a surface with specific polymeric micelles of the present invention imparts several advantages to the coated surface. More specifically, the present inventors have found that coated surfaces, especially multi-layered coated surfaces, with polymeric micelles of the type described hereinbelow enhances the ability of the coated surface to retain water, prevents penetration of proteins and lipids therethrough and enhances drug delivery capabilities of the coated surface.